A subset of homozygous PiZZ alpha1-AT-deficient individuals is more susceptible to liver injury by virtue of a second inherited traits, or facts which exaggerates the intracellular accumulation of mutant alpha1- AT, or exaggerates the cellular pathophysiologic consequences of mutant alpha1-AT accumulation. Identification of this trait or traits may allow predictive testing for susceptibility to liver disease as well as novel approaches for pharmacologic amelioration of the liver injury.